We administered ProMACE-CytaBom chemotherapy followed by the immunoconjugate, anti-B4-blocked ricin, to advanced stage indolent lymphoma patients both untreated and with limit previous therapy in an attempt to achieve high complete response and prolong disease-free survival. Study endpoints include clinical/pathological responses as well as molecular complete responses as determined by polymerase chain reaction analysis of sequential bone marrow samples. Currently, 40 patients have been entered on study. Eleven continue on ProMACE-CytaBom chemotherapy and are too early to evaluate. One patient developed a second malignancy while on study. Lymphoma treatment was stopped and the patient died of progressive disease due to her solid tumor and is not evaluable for response. Among the 29 patients evaluable for response to chemotherapy: 20 achieved a complete response (69%). One patient had progressive disease on chemotherapy, came off study and was treated with other therapy, but died of progressive lymphoma. Twenty-five patients have gone on to receive alphaB4-blocked ricin. Following the immunotoxin therapy, 7/20 (35%) complete responders have relapsed after short remissions; two have required immediate retreatment and the others are being followed with disease. The toxicities observed with the immunotoxin therapy include the expected flu-like symptoms: fatigue, myalgias, fever, chills, headache, and edema. No patient has required dose-reduction for liver function abnormalities or reduced platelet count. Two patients, both females taking estrogen replacement did, however develop a pulmonary embolism while on the alphaB4-blocked ricin. They are the only two cases of reported a pulmonary embolism on this therapy. We have since stopped estrogen replacement in women before beginning the immunotoxin and have not seen other embolisms.